Enhancement of the efficacy of triazolopyrimidines

ABSTRACT

The present invention relates to a method for the enhancement of the potency, systemicity, and breadth of spectrum of a fungicidal composition containing a triazolopyrimidine fungicide which comprises adding to said composition a fungicidally-enhancing amount of an adjuvant selected from the group consisting of a non-ionic water-soluble mixed polyalkoxylated aliphatic alcohol surfactant; a non-ionic water-soluble ethoxylated aliphatic alcohol surfactant; an amine ethoxylate; a micronized polymeric wax; and a mixture thereof.

BACKGROUND OF THE INVENTION

[0001] As a rule, inert carrier ingredients must be used to bring cropprotection agents, for example, fungicidal agents, into a form such thatthe user can apply said agents either directly or after dilution withwater. The choice of formulation type and inert ingredients oftendetermines to a significant extent whether said agent can display itsfull activity upon application.

[0002] The efficacy of the crop protection agent can often be improvedby the addition of other crop protection agents. The observed efficacyof the combination of crop protection agents can sometimes besignificantly higher than that which would be expected from the amountsof the individual agents used, thus indicating synergism from the activecomponents of the combination.

[0003] The usual components of formulations such as carriers and inertingredients (e.g. organic solvents, suspension agents, emulsion agents,wetting agents, solubilizing agents) which do not themselves possessbiological activity, however, do not usually lead to an unexpectedincrease in efficacy.

[0004] Triazolopyrimidine compounds and their fungicidal use aredescribed in U.S. Pat. Nos. 4,567,263; 5,593,996; and 5,756,509, amongother publications. The enhancement of the fungicidal efficacy of saidtriazolopyrimidines by the addition of selected adjuvants is describedin EP 943,241. However, there is a need for continued effort to discoversuitable adjuvants which when used in combination with atrizaolopyrimidine fungicide provide a means to lower the dose of saidfungicide required for effective disease control.

[0005] Therefore, it is an object of this invention to provide a methodfor the enhancement of the efficacy of a triazolopyrimidine fungicidecomposition.

[0006] It is another object of this inventions to provide an economic,efficient and environmentally compatable method for the control ofphytopathogenic disease.

[0007] It is a further object of this invention to provide a fungicidalcomposition having enhanced potency, systemicity and breadth of spectrumof disease control.

[0008] These and other objects and features of the invention will becomeapparent from the detailed description set forth herein below.

SUMMARY OF THE INVENTION

[0009] The present invention provides a method for the enhancement ofthe fungicidal activity of a composition containing a triazolopyrimidinefungicide which method comprises adding to said composition an adjuvantselected from the group consisting of

[0010] a) a non-ionic water-soluble mixed polyalkoxylated aliphaticalcohol surfactant;

[0011] b) a non-ionic water-soluble ethoyxlated aliphatic alcoholsurfactant;

[0012] c) an amine ethoyxlate;

[0013] d) a micronized polymeric wax; and

[0014] e) a mixture thereof.

[0015] The present invention also provides fungicidal compositions andmethods of phytopathogenic fungal disease control.

DETAILED DESCRIPTION OF THE INVENTION

[0016] Due to the continual risk of disease resistance and ecologicalconcerns over dosage levels of pesticides, there is ongoing research toidentify suitable adjuvants which when used in combination with abiologically active agent, such as a fungicide, will provide a means tolower the dose of said fungicide required for effective disease control.

[0017] It has now been found that compositions containing atriazolopyrimidine fungicide when applied in combination with one ormore adjuvants selected from the group consisting of

[0018] a) a non-ionic water-soluble mixed polyalkoxylated aliphaticalcohol surfactant;

[0019] b) a non-ionic water-soluble ethoxylated aliphatic alcoholsurfactant;

[0020] c) an amine ethoxylate;

[0021] d) a micronized polymeric wax; and

[0022] e) a mixture thereof demonstrate enhanced potency, systemicityand increased breadth of spectrum of disease control.

[0023] The term adjuvant as used in the specification and claimsdesignates a substance which can increase the biological activity of anactive ingredient but is not itself significantly biologically active.

[0024] Triazolopyrimidine fungicides contemplated for use in the methodof invention are those compounds of the triazolopyrimidine class ofchemistry which demonstrate in vivo and in vitro fungicidal activity.Said fungicides are known in the art and descriptions thereof may befound in, for example, in U.S. Pat Nos. 4,567,263; 5,593,996; and5,756,509, among other publications.

[0025] Preferred triazolopyrimidine fungicides suitable for use in theinventive method are compounds of formula I

[0026] wherein

[0027] R₁ and R₂ each independently represent hydrogen or an optionallysubstituted alkyl, alkenyl, alkynyl, alkadienyl, haloalkyl, aryl,heteroaryl, cycloalkyl, bicycloalkyl or heterocyclyl group, or

[0028] R₁ and R₂ together with the adjacent nitrogen atom represent anoptionally substituted heterocyclic ring;

[0029] R₃ represents a halogen atom or an alkyl or alkoxy group;

[0030] n represents an inter of 0 to 5; and

[0031] Hal represents a halogen atom.

[0032] More preferred triazolopyrimidine fungicides are those compoundsof formula I wherein

[0033] R₁ represents C₁-C₆alkyl, C₁-C₆haloalkyl, or a C₃-C₈cycloalkylgroup;

[0034] R₂ represents a hydrogen atom or a C₁-C₆alkyl group or

[0035] R₁ and R₂ together with the adjacent nitrogen atom represent anoptionally substituted 6-membered heterocyclic ring;

[0036] R₃ represents a chlorine or fluorine atom;

[0037] n represents an integer of 2 or 3; and

[0038] Hal represents a chlorine atom.

[0039] Particularly preferred fungicides are those triazolopyrimidinecompounds of formula I wherein R₁ represents C₁-C₆fluoroalkyl; R₂represents a hydrogen atom; R₃ represents a chlorine or a fluorine atom;and n represents an integer of 3.

[0040] The non-ionic water-soluble mixed polyalkoxylated or ethoxylatedaliphatic alcohol adjuvant suitable for use in the method of theinvention is Plurafac® LF 300, commercially available fromTensid-chemie, Köln, Germany or BASF AG, Ludwigshafen, Germany.

[0041] Non-ionic water-soluble polyethoxylated surfactants suitable foruse in the method of the invention are straight-chained or branchedC₁₀-C₂₅alcohols ethoxylated with 10 to 25 ethoxy groups. A preferredpolyethoxylated surfactant is Lubrol® 17A17, commercially available fromUniqema, Everberg, Belgium.

[0042] Amine ethoxylate adjuvants suitable for use in the inventivemethod are tertiary amine ethoxylates based on primary amines such asoleyl amine and tallow amine. Preferred amine ethoxylates are thosecommercially available under the trademark Berol 381®, Berol 303®, andEthomeen® S22 (Akzo Nobel Surface Chemistry, Sweden).

[0043] Among the micronized polymeric waxes suitable for use in themethod of the invention is a modified polyethylene wax commerciallyavailable under the trademark Ceridust® 9615A (Clariant GmBH, Augsburg,Germany).

[0044] The adjuvants of the present invention may be included in thetriazolopyrimidine fungicidal composition or added separately in a tankmix. When being tank-mixed, said adjuvants may be added with othercomponents such as a dispersing agent or an antifoam agent, and, wheredesirable, with further adjuvants so as to ensure that they arehomogeneously dispersed in the tank mix.

[0045] The present invention also provides a fungicidal compositionwhich comprises a triazolopyrimidine fungicide and afungicidally-enhancing amount of an adjuvant selected from the groupconsisting of

[0046] a) a non-ionic water-soluble mixed polyalkoxylated aliphaticalcohol surfactant;

[0047] b) a non-ionic water-soluble ethoxylated aliphatic alcoholsurfactant;

[0048] c) an amine ethoxylate;

[0049] d) a micronized polymeric wax; and

[0050] e) a mixture thereof.

[0051] Preferred triazolopyrimidine fungicides suitable for use in thecomposition of the invention are compounds of formula I

[0052] wherein R₁, R₂, R₃, n and Hal are as defined hereinabove.

[0053] In general, fungicidally-enhancing amounts of the adjuvant arepresent in a wt/wt ratio of triazolopyrimidine fungicide to adjuvant ofabout 1.0:0.75 to 1.0:1,000, preferably about 1.0:0.9 to 1.0:500, morepreferably, about 1.0:1.25 to 1.0:50. It has been found that in general,fimgicidal efficacy may be enhanced to a higher degree by the additionof larger amounts of the adjuvant.

[0054] The recommended dose rates for various applications of thetriazolopyrimidine fungicide are known. Advantageously, the inventivecomposition may (depending on the particular triazolopyrimidinefungicide, the adjuvant and their amounts) reduce the amount of saidfungicide required per hectare by half or more, thereby enhancing thebreadth of disease control at a reasonable dose rate.

[0055] Although dose rates may vary according to prevailing conditionssuch as mode of application, degree and type of fungal infection, targetcrop species, weather conditions, or the like, compositions of theinvention may be applied at rates of about 40 to 4000 ml/ha, preferablyabout 50 to 3000 ml/ha, more preferably about 60 to 2000 ml/ha.

[0056] Surprisingly, the composition of the invention demonstrates rapidonset and high persistency of activity. These properties enlarge theperiod for application of the fungicide and, hence, increases itsutility in the field. Advantageously, the fungicidal compositions of theinvention may be used both prophylactically and curatively.

[0057] Aqueous dispersions and emulsions, for example compositionsobtained by diluting the formulated product according to the inventionwith water, also lie within the scope of the invention.

[0058] The adjuvants according to the invention, the triazolopyrimidinefungicides and usual adjuvants and carriers may be formulated as any oneof the conventional fluid or dispersible solid formulations known in theart, for example, as a solution, an emulsion, a wettable powder, asuspension concentrate, an emulsion concentrate, a low volume or ultralow volume preparation, a water dispersible granule, or any otherconventional form known to be suitable for agricultural andhorticultural applications.

[0059] Fluid or solid carriers or solubilising agents such as organicsolvents, i.e. ketones, alcohols, fluid aliphatic, aliphatic or aromaticcompounds, fine natural or synthetic silicates or carbonates; ionic ornon-ionic surfactants which function as emulsion, dispersing or wettingagents; antifoam and antifreeze agents; or any suitable adjuvant andcarrier substances which are described in the literature may be includedin the inventive composition.

[0060] A carrier which will provide slow release of the pesticidalcompounds into the environment of the target plant is particularlysuitable for use in the composition of the invention.

[0061] The present invention also provides a method for the enhancedcontrol of phytopathogenic fungi which comprises applying to the locusof said fungi an effective amount of a composition containing atriazolopyrimidine fungicide and a fungicidally-enhancing amount of anadjuvant selected from the group consisting of

[0062] a) a non-ionic water-soluble mixed polyalkoxylated aliphaticalcohol surfactant;

[0063] b) a non-ionic water-soluble ethoxylated aliphatic alcoholsurfactant;

[0064] c) an amine ethoxylate;

[0065] d) a micronized polymeric wax; and

[0066] e) a mixture thereof.

[0067] Plant diseases which may be combated with the method of theinvention include diseases caused by Ascomycete fungi, such asErysiphales, for example Erysiphe cichoracearum or Uncinula necator; orDothideales, for example Venturia inaequalis or Septoria tritici(Mycosphaerella graminicola).

[0068] For a more clear understanding of the invention, specificexamples thereof are set forth herein below. These examples are merelyillustrative, and are not to be understood as limiting the scope andunderlying principles of the invention in any way.

EXAMPLE 1 Evaluation of the Curative and Residual Fungicidal ActivityObtained by the Application of a Triazolopyrimidine Composition Plus anAdjuvant or Mixture of Adjuvants

[0069] The triazolopyrimidine composition used in this evaluation isprepared as an aqueous suspension concentrate having concentrations of100, 20, and 4 ppm active ingredient. The composition is tank-mixed withfrom 0 ppm to 1,000 ppm of an adjuvant, or mixture of adjuvants, andapplied to greenhouse plants using a single-nozzle overhead tracksprayer at an application rate of 200 litre/ha. When two adjuvants areadded to the composition, the concentration of each adjuvant is 500 ppm.

[0070] Barley seedlings (var. ‘Golden Promise’) and wheat seedlings(var. ‘Kanzler’) are grown to the primary leaf stage (ca. 1 week old) in6-cm-diameter pots in the greenhouse. Plants for both curative andresidual tests are sprayed at the same time and inoculations of thepathogens are done on different days.

[0071] For curative tests, barley and wheat plants are inoculated 2 daysprior to test composition treatment by dusting with conidia of Blumeria(Erysiphe) graminis f.sp. hordei or B. graminis f.sp. tritici to createpowdery mildew diseases. Plants are kept in the greenhouse untiltreated. After treatment, the plants are kept until powdery mildewdisease symptoms develop on untreated plants. Plants are then evaluatedfor percent disease on the treated primary leaves. For curative rusttests, wheat plants are inoculated 2 days prior to test compositiontreatment by spraying with a urediniospore suspension in 0.05% aqueousTween® 20 (1 mg spores per ml) of Puccinia recondita, and kept in amoist infection chamber for one day. After treatment, the plants arekept in the greenhouse until disease symptoms develop on untreatedplants. Plants are then evaluated for percent disease on the treatedprimary leaves.

[0072] For residual tests, plants are treated first and then kept for 4days in the greenhouse before being inoculated with the pathogens asdescribed for curative tests. Inoculated plants are kept in thegreenhouse until disease symptoms develop on untreated plants. Plantsare then evaluated for percent disease on the treated primary leaves.

[0073] Disease control is calculated using the following formula:${\% \quad \text{disease control}} = {100 - \frac{\% \quad \text{infected leaf area in treated plants}}{\% \quad \text{infected leaf area in untreated plants}}}$

[0074] The mean values for the % control of the three concentrations ofactive ingredient is reported in Table I. The adjuvant concentrationsare the same at all the concentrations used.

[0075] As can be seen from the data shown on Table I, the addition ofone or more adjuvants to a triazolopyrimidine fungicide compositionaccording to the method of the invention significantly enhances thefungicidal activity of said composition.

Acative Ingredient Employed

[0076] CompoundIA=5-Chloro-7-[(2,2,2-trifluoro-1-methylethyl)amino]-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5a]pyrimidine. ADJUVANTS EMPLOYED Commercial ProductDescription Plurafac ® LF300, non-ionic water-soluble mixed (BASF;Ludwigshafen, Germany) polyalkoyxlated aliphatic alcohol surfactantLubrol ® 17A17 non-ionic water-soluble ethoxylated (Uniqema; Evergerg,Belgium aliphatic alcohol surfactant Berol ® 381 amine ethoxylate (AkzoNobel; Sweden) Ethomeen ® S22 amine ethoxylate (Akzo Nobel; Sweden)Ceridust ® 9615A micronized polymeric wax (Clariant GMBH; Augsberg,Germany) Composition A: Suspension Concentrate Component Amount [g/l]Ingredient triazolopyrimidine 100.0  Compound IA fungicide dispersant20.0  Atlas G5000¹ dispersant 10.0  Synperonic A7¹ antifoam agent 3.0Rhodorsil ® 426 R² preservative 2.0 Proxel ® GXL³ surfactant 3.0Rhodopol ® 23² antifreeze agent 50.0  propylene glycol water to 1000 ml

[0077] TABLE I % Disease Control WPM* WLR* BPM* 2 Day 4 Day 2 Day 4 Day2 Day 4 Day TREATMENT Curative Residual Curative Residual CurativeResidual Composition A 16 42 48 10 21 14 Composition A 49 40 69 28 69 30& Plurafac LF 300 (1000 ppm) Composition A & Lubrol 17A17 43 33 72 15 3826 (1000 ppm) Composition A 42 40 79 33 38 28 & Plurafac LF 700 (500ppm)& Lubrol 17A17 (500 ppm) Composition A 55 49 78 38 57 43 & PlurafacLF 300 (500 ppm)& Lubrol 17A17 (500 ppm) Composition A 52 47 72 23 54 38& Berol 381 (1000 ppm) Composition A 53 48 72 22 56 28 & Ethomeen S22(1000 ppm) Composition A 29 45 62 27 35 32 & Ceridust 9615A (1000 ppm)

What is claimed is:
 1. A method for the enhancement of the fungicidalactivity of a composition containing a triazolopyrimidine fungicidewhich method comprises adding to said composition an adjuvant selectedfrom the group consisting of a) a non-ionic water-soluble mixedpolyalkoxylated aliphatic alcohol surfactant; b) a non-ionicwater-soluble ethoxylated aliphatic alcohol surfactant; c) an amineethoxylate; d) a micronized polymeric wax; and e) a mixture thereof. 2.The method according to claim 1 wherein said adjuvant is present in awt/wt ratio of adjuvant to triazolopyrimidine fungicide of about1.0:0.75 to 1.0:1,000.
 3. The method according claim 2 wherein saidratio is about 1.0:0.9 to 1.0:500.
 4. The method according to claim 3wherein said ratio is about 1.0:1.25 to 1.0:50.
 5. The method accordingto claim 1 wherein said triazolopyrimidine fungicide is a compound offormula I.

wherein R₁ and R₂ each independently represent hydrogen or an optionallysubstituted alkyl, alkenyl, alkynyl, alkadienyl, haloalkyl, aryl,heteroaryl, cycloalkyl, bicycloalkyl or heterocyclyl group, or R₁ and R₂together with the adjacent nitrogen atom represent an optionallysubstituted heterocyclic ring; R₃ represents a halogen atom or an alkylor alkoxy group; n represents an integer of 0 to 5; and Hal represents ahalogen atom.
 6. The method according to claim 1 wherein saidcomposition is a suspension concentrate composition.
 7. The methodaccording to claim 6 wherein said adjuvant is a non-ionic water-solublemixed polyalkoxylated aliphatic alcohol surfactant, a non-ionicwater-soluble ethoxylated aliphatic alcohol surfactant or a mixturethereof.
 8. The method according to claim 7 wherein said ethoxylatedalcohol surfactant is an aliphatic C₁₀-C₂₅ alcohol ethoxylated with 10to 25 ethoxy groups.
 9. The method according to claim 7 wherein saidmixed polyalkoxylated alcohol surfactant is Plurafac® LF
 300. 10. Afungicidal composition which comprises a triazolopyrimidine fungicideand a fungicidally-enhancing amount of an adjuvant selected from thegroup consisting of a) a non-ionic water-soluble mixed polyalkoxylatedaliphatic alcohol surfactant; b) a non-ionic water-soluble ethoxylatedaliphatic alcohol surfactant; c) an amine ethoxylate; d) a micronizedpolymeric wax; and e) a mixture thereof.
 11. The composition accordingto claim 10 wherein the triazolopyrimidine fungicide is a compound offormula I

wherein R₁ and R₂ each independently represent hydrogen or an optionallysubstituted alkyl, alkenyl, alkynyl, alkadienyl, haloalkyl, aryl,heteroaryl, cycloalkyl, bicycloalkyl or heterocyclyl group, or R₁ and R₂together with the adjacent nitrogen atom represent an optionallysubstituted heterocyclic ring; R₃ represents a halogen atom or an alkylor alkoxy group; n represents an integer of 0 to 5; and Hal represents ahalogen atom.
 12. The composition according to claim 10 wherein thenon-ionic water-soluble mixed polyalkoxylated aliphatic alcoholsurfactant is Plurafac® LF
 300. 13. The composition according to claim10 wherein said fungicide and said adjuvant are present in a wt/wt ratioof fungicide to adjuvant of about 1.0:0.75 to 1.0:1,000.
 14. Thecomposition according to claim 13 wherein said ratio is about 1.0:0.9 to1.0:500.
 15. The composition according to claim 14 wherein said ratio isabout 1.0:1.25 to 1.0:50.
 16. A method for the enhanced control ofphytopathogenic fungi which comprises applying to the lous of said fungian effective amount of a composition having triazolopyrimidine fungicideand a fungicidally-enhancing amount of an adjuvant selected from thegroup consisting of a) a non-ionic water-soluble mixed polyalkoxylatedaliphatic alcohol surfactant; b) a non-ionic water-soluble ethoxylatedaliphatic alcohol surfactant; c) an amine ethoxylate; d) a micronizedpolymeric wax; and e) a mixture thereof.
 17. The method according toclaim 16 wherein said fungi is Ascomyte fungi.
 18. The method accordingto claim 16 wherein said fungi is Dothidales or Erysiphales fungi. 19.The method according to claim 16 wherein the non-ionic water-solublemixed polyalkoxylated aliphatic alcohol surfactant is Plurafac® LF 300.20. The method according to claim 19 wherein said triazolopyrimidinefungicide is5-chloro-7-[(2,2,2-trifluoro-1-methylethyl)amino]-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5a]pyrimidine.